Determination of (R)-(+)- and (S)-(−)-Nicotine Chirality in Puff Bar E-Liquids by 1H NMR Spectroscopy, Polarimetry, and Gas Chromatography–Mass Spectrometry

Duell, Anna K; Kerber, Paul J; Luo, Wentai; Peyton, David H.

doi:10.1021/acs.chemrestox.1c00192

Cited by 19 publications

(38 citation statements)

References 16 publications

(33 reference statements)

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“…Studies enabling the testing of products for synthetic versus tobacco nicotine, such as the determination of the enantiomeric excess of the synthetic enantiomers, are needed for validating industry claims that they are not using TDN 41–43. However, the distinction between synthetic and TDN has become more challenging, as new laboratory syntheses of enantiomerically pure nicotine have recently been patented 1.…”

Section: New Ends Products and Research Agendasmentioning

confidence: 99%

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Emerging ENDS products and challenges in tobacco control toxicity research

et al. 2022

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Electronic nicotine delivery systems (ENDS) continue to rapidly evolve. Current products pose unique challenges and opportunities for researchers and regulators. This commentary aims to highlight research gaps, particularly in toxicity research, and provide guidance on priority research questions for the tobacco regulatory community. Disposable flavoured ENDS have become the most popular device class among youth and may contain higher nicotine levels than JUUL devices. They also exhibit enhanced harmful and potentially harmful constituents production, contain elevated levels of synthetic coolants and pose environmental concerns. Synthetic nicotine and flavour capsules are innovations that have recently enabled the circumvention of Food and Drug Administration oversight. Coil-less ENDS offer the promise of delivering fewer toxicants due to the absence of heating coils, but initial studies show that these products exhibit similar toxicological profiles compared with JUULs. Each of these topic areas requires further research to understand and mitigate their impact on human health, especially their risks to young users.

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Section: New Ends Products and Research Agendasmentioning

confidence: 99%

“…For synthetic products containing both nicotine enantiomers,42 an issue is that human exposure to ( R )-(+)-nicotine has been relatively minimal to date, since it is present in tobacco at levels of just 0.1%–1.2%. In addition, it has proved challenging to purify.…”

Section: New Ends Products and Research Agendasmentioning

confidence: 99%

Emerging ENDS products and challenges in tobacco control toxicity research

et al. 2022

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“…The Puff Bar website states that “All Puff Bar products listed on this website contain nicotine but do not contain tobacco or anything derived from tobacco. Puff Bar products are not intended for use with any tobacco product or any component or part of a tobacco product.” A study by Duell et al examined both early and current Puff Bar products, concluding that they did switch from TDN to SyN [ 4 ]. The authors found that the older Puff Bar products contained >99% ( S )-nicotine, whereas the newer SyN-containing Puff Bars contained both ( R )- and ( S )-isomers in a ~1:1.2 ratio, inconsistent with a racemic SyN being used (see Scientific Context below).…”

Section: Introductionmentioning

confidence: 99%

Analysis and differentiation of tobacco-derived and synthetic nicotine products: Addressing an urgent regulatory issue

Cheetham¹,

Plunkett²,

Campbell³

et al. 2022

PLoS ONE

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There is significant regulatory and economic need to distinguish analytically between tobacco-derived nicotine (TDN) and synthetic nicotine (SyN) in commercial products. Currently, commercial e-liquid and oral pouch products are available that contain tobacco-free nicotine, which could be either extracted from tobacco or synthesized. While tobacco products that contain TDN are regulated by FDA Center for Tobacco Products, those with SyN are currently not in the domain of any regulatory authority. This regulatory difference provides an economic incentive to use or claim the use of SyN to remain on the market without submitting a Premarket Tobacco Product Application. TDN is ~99.3% (S)-nicotine, whereas SyN can vary from racemic (50/50 (R)/(S)) to ≥ 99% (S)-nicotine, i.e., chemically identical to the tobacco-derived compound. Here we report efforts to distinguish between TDN and SyN in various samples by characterizing impurities, (R)/(S)-nicotine enantiomer ratio, (R)/(S)-nornicotine enantiomer ratio, and carbon-14 (14C) content. Only 14C analysis accurately and precisely differentiated TDN (100% 14C) from SyN (35–38% 14C) in all samples tested. 14C quantitation of nicotine samples by accelerator mass spectrometry is a reliable determinate of nicotine source and can be used to identify misbranded product labelled as containing SyN. This is the first report to distinguish natural, bio-based nicotine from synthetic, petroleum-based nicotine across a range of pure nicotine samples and commercial e-liquid products.

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“…2 Various methods have been reported in the literature for the evaluation of enantiomeric composition of nicotine. [3][4][5][6][7][8][9][10][11][12][13] Some of these studies used a Gas Chromatography (GC) separation with Mass Spectroscopy (MS) detection on two connected columns, a Cyclodex B (J&W Scientific) and a Rt-BDEXsm (Restek), 3,4 or two Rt-GammaDEXsa (Restek), 5 or on one column Chiral Cyclodex B (Agilent Technol.). 6 However, the separation of enantiomers by these procedures did not exhibit baseline resolution.…”

Section: Introductionmentioning

confidence: 99%

“…This interest has been emphasized mainly because vaping became popular, and some vaping companies started using synthetic nicotine in their products with the ratio of (S) ‐ and (R) ‐nicotine varying from 50/50 racemic, to very low (R) ‐nicotine content 2 . Various methods have been reported in the literature for the evaluation of enantiomeric composition of nicotine 3–13 . Some of these studies used a Gas Chromatography (GC) separation with Mass Spectroscopy (MS) detection on two connected columns, a Cyclodex B (J&W Scientific) and a Rt‐BDEXsm (Restek), 3,4 or two Rt‐GammaDEXsa (Restek), 5 or on one column Chiral Cyclodex B (Agilent Technol.)…”

Section: Introductionmentioning

confidence: 99%

Interconversion of nicotine enantiomers during heating and implications for smoke from combustible cigarettes, heated tobacco products, and electronic cigarettes

Moldoveanu

2022

Chirality

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Physiological properties of (R)‐nicotine have differences compared with (S)‐nicotine, and the subject of (S)‐ and (R)‐nicotine ratio in smoking or vaping related items is of considerable interest. A Liquid Chromatography‐Mass Spectrometry/Mass Spectrometry (LC‐MS/MS) method for the analysis of (S)‐ and (R)‐nicotine has been developed and applied to samples of nicotine from different sources, nicotine pyrolyzates, several types of tobacco, smoke from combustible cigarettes, smoke from heated tobacco products, e‐liquids, and particulate matter obtained from e‐cigarettes aerosol. The separation was achieved on a Chiracel OJ‐3 column, 250 × 4.6 mm with 3‐μm particles using a nonaqueous mobile phase. The detection was performed using atmospheric pressure chemical ionization (APCI) in positive mode. The only transition measured for the analysis of nicotine was 163.1 → 84.0. The method has been summarily validated. For the analysis, the samples of tobacco and smoke from combustible cigarettes were subject to a cleanup procedure using solid phase extraction (SPE). It was demonstrated that nicotine upon heating above 450°C for several minutes starts decomposing, and some formation of (R)‐enantiomer from a sample of 99% (S)‐nicotine is observed. An analogous process takes place when a 99% (R)‐nicotine is heated and forms low levels of (S)‐nicotine. This interconversion has the effect of slightly increasing the content of (R)‐nicotine in smoke compared with the level in tobacco for combustible cigarettes and for heated tobacco products. The (S)/(R) ratio of nicotine enantiomers in e‐liquids was identical with the ratio for the particulate phase of aerosols generated by e‐cigarette vaping.

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Determination of (R)-(+)- and (S)-(−)-Nicotine Chirality in Puff Bar E-Liquids by ¹H NMR Spectroscopy, Polarimetry, and Gas Chromatography–Mass Spectrometry

Cited by 19 publications

References 16 publications

Emerging ENDS products and challenges in tobacco control toxicity research

Emerging ENDS products and challenges in tobacco control toxicity research

Analysis and differentiation of tobacco-derived and synthetic nicotine products: Addressing an urgent regulatory issue

Interconversion of nicotine enantiomers during heating and implications for smoke from combustible cigarettes, heated tobacco products, and electronic cigarettes

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